Isoflurane anesthesia is bad for demented rats

We know that about 20% of elderly patients have Postoperative Cognitive Dysfunction (POCD) after surgery but we still don’t know what the link, if any, is to general anesthesia. This February 2008 study in the journal Anesthesia & Analgesia provides laboratory evidence that anesthesia might hasten the onset of Alzheimer’s in genetically susceptible patients.

Researchers at the University of Pennsylvania took rat brain cells and introduced a genetic mutation associated with Alzheimers called PS1. The cells with the presenilin-1 mutation, when exposed to isoflurane, showed various signs of injury, including an increase in the concentration of calcium inside the cell, and an increase in the concentration of the enzyme LDH. This injury was not seen in the cells without the mutation.

Interestingly, cells exposed to two other commonly used anesthetics, sevoflurane and desflurane, did not show the same signs of cell injury.

The conclusion is that a known risk factor for early Alzheimer’s disease increases the vulnerability of brain cells to clinical concentrations of isoflurane.

Several other studies have shown evidence of apoptosis – “programmed cell death” – induced by isoflurane, as well as effects on amyloid, a brain protein associated with Alzheimer’s.

This is an animal (rat) study, so we cannot say that isoflurane is harmful to humans who have Alzheimer’s.

Isoflurane is an anesthetic with a long track record of safety. It may even, paradoxically, be protective of brain cells at lower doses given over shorter time periods, and can be cardioprotective too.

No studies have yet been done, but drugs like dantrolene, which block the release of calcium inside cells could perhaps protect high risk elderly patients from the possible harmful effects of isoflurane anesthesia, such as POCD. More research is definitely needed.


A presenilin-1 mutation renders neurons vulnerable to isoflurane toxicity. Anesth Analg. 2008 Feb;106(2):492-500.

One Response to Isoflurane anesthesia is bad for demented rats

  1. Anonymous says:

    […] A brain monitor could be used to prevent awareness – the under-dosing problem of which we are so fearful. It could also be used to fine tune the amount of anesthesia so that relative “overdosing” is avoided. Overdosing is costly (increased anesthetic drug costs, increased recovery time) and might even be bad for the brain (postoperative cognitive dysfunction). […]

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: